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A neuronal nitric oxide synthase (NOS-I) haplotype associated with schizophrenia modifies prefrontal cortex function.

A Reif1, S Herterich, A Strobel

  • 1Department of Psychiatry and Psychotherapy (Section for Clinical and Molecular Psychobiology and Laboratory for Psychophysiology and Functional Imaging), Julius-Maximilians-University Würzburg, Würzburg, Germany. a.reif@gmx.net

Molecular Psychiatry
|January 4, 2006
PubMed
Summary

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Regulatory polymorphisms in the NOS1 gene are linked to schizophrenia (SCZ) and bipolar disorder, influencing prefrontal brain function. These genetic variations may increase psychosis risk.

Area of Science:

  • Neuroscience
  • Genetics
  • Psychiatry

Background:

  • Nitric oxide (NO) acts as a neurotransmitter and interacts with dopamine and serotonin systems.
  • The NOS-I gene (NOS1) is located on chromosome 12q24.2, a region linked to schizophrenia and bipolar disorder.

Purpose of the Study:

  • To investigate if NOS1 gene polymorphisms contribute to the genetic risk of schizophrenia and bipolar disorder.
  • To examine the association between NOS1 polymorphisms and psychopathology and prefrontal functioning.

Main Methods:

  • Genotyping of five NOS1 polymorphisms and a NOS1 mini-haplotype in 195 schizophrenic patients, 72 bipolar patients, and 286 controls.
  • Analysis of associations between polymorphisms, disease status, psychopathology, and prefrontal function (neuropsychological tests, Go-Nogo paradigm).

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Main Results:

  • The exon 1c promoter polymorphism of NOS1 was associated with schizophrenia (SCZ).
  • Long promoter alleles of a repeat polymorphism correlated with less severe psychopathology.
  • A NOS1 mini-haplotype showed a significant association with SCZ.
  • Regulatory NOS1 polymorphisms, not coding variants, appear to confer genetic risk for psychosis.
  • Promoter polymorphisms affected prefrontal functioning in patients.

Conclusions:

  • Regulatory polymorphisms in the NOS1 gene contribute to the genetic risk for schizophrenia.
  • These NOS1 variants modulate prefrontal brain function, impacting cognitive and electrophysiological parameters.